Loss of Major DNase I Hypersensitive Sites in Duplicated β-globin Gene Cluster Incompletely Silences HBB Gene Expression
Language English Country United States Media print-electronic
Document type Case Reports, Journal Article, Research Support, Non-U.S. Gov't
PubMed
27492747
DOI
10.1002/humu.23061
Knihovny.cz E-resources
- Keywords
- HBB duplication, globin genes, regulation, sickle cell disease,
- MeSH
- 3' Flanking Region MeSH
- beta-Globins genetics MeSH
- Genes, Duplicate * MeSH
- Transcription, Genetic MeSH
- Infant MeSH
- Humans MeSH
- Mutation MeSH
- Locus Control Region MeSH
- Anemia, Sickle Cell genetics MeSH
- Gene Silencing MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- beta-Globins MeSH
We report an infant with sickle cell disease phenotype by biochemical analysis whose β-globin gene (HBB) sequencing showed sickle cell mutation (HBBS ) heterozygosity. The proband has a unique head-to-tail duplication of the β-globin gene cluster having wild-type (HBBA ) and HBBS alleles inherited from her father; constituting her HBBS /HBBS -HBBA genotype. Further analyses revealed that proband's duplicated β-globin gene cluster (∼650 kb) encompassing HBBA does not include the immediate upstream locus control region (LCR) or 3' DNase I hypersensitivity (HS) element. The LCR interacts with β-globin gene cluster involving long range DNA interactions mediated by various transcription factors to drive the regulation of globin genes expression. However, a low level of HBBA transcript was clearly detected by digital PCR. In this patient, the observed transcription from the duplicated, distally displaced HBBA cluster demonstrates that the loss of LCR and flanking 3'HS sites do not lead to complete silencing of HBB transcription.
Center for Cancer and Blood Disorders Nemours El Dupont Hospital for Children Wilmington Delaware
Department of Biology Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Molecular Pathology Viapath at King's College Hospital NHS Foundation Trust London UK
Department of Pathology School of Medicine University of Utah Salt Lake City Utah
Institute for Clinical and Experimental Pathology ARUP Laboratories Salt Lake City Utah
References provided by Crossref.org
